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吡罗昔康-铜配合物:体内对多形核白细胞向铜绿假单胞菌趋化因子迁移的抑制作用及体外超氧化物歧化酶样活性

Piroxicam-copper complexes: inhibition of polymorphonuclear leukocyte migration to Pseudomonas aeruginosa chemotactins in vivo and superoxide dismutase-like activity in vitro.

作者信息

Sordelli D O, Fontán P A, Amura C R

机构信息

Departamento de Microbiología, Parasitología e Immunología, Facultad de Medicina, Universidad de Buenos Aires, Argentina.

出版信息

Agents Actions. 1993 Mar;38(3-4):196-201. doi: 10.1007/BF01976211.

DOI:10.1007/BF01976211
PMID:8213346
Abstract

Piroxicam-copper (Cu2+) complexes, formed spontaneously by mixing solutions of piroxicam and CuSO4 (1:1 Cu2+:piroxicam), inhibited the superoxide anion-catalyzed reduction of ferricytochrome C in a dose-related fashion. Addition of ethylenediaminetetraacetate to the mixture decreased in a dose-related manner the superoxide dismutase (SOD)-like activity of piroxicam-Cu2+. Piroxicam alone (10(-5) M, final concentration) did not display SOD-like activity but 10(-5) M Cu2+ exhibited significant activity, similar to that of piroxicam-Cu2+. Intraperitoneal treatment of mice with either 0.64 mg/kg piroxicam or its Cu2+ complexes (0.64 mg/kg piroxicam + 0.12 mg/kg Cu2+) was equally effective in diminishing both the migration of polymorphonuclear leukocytes (PMNL) to the airways and the content of myeloperoxidase activity in the lungs, induced by aerosol challenge with Pseudomonas aeruginosa peptide chemotactins. Therefore, piroxicam-Cu2+ complexes may provide both the anti-inflammatory activity of piroxicam plus the SOD-like activity of Cu2+.

摘要

吡罗昔康与铜(Cu2+)的络合物由吡罗昔康溶液和CuSO4(Cu2+与吡罗昔康比例为1:1)混合自发形成,它以剂量相关的方式抑制超氧阴离子催化的铁细胞色素C还原。向混合物中加入乙二胺四乙酸以剂量相关的方式降低了吡罗昔康 - Cu2+的超氧化物歧化酶(SOD)样活性。单独的吡罗昔康(终浓度为10(-5) M)不显示SOD样活性,但10(-5) M Cu2+表现出显著活性,类似于吡罗昔康 - Cu2+的活性。用0.64 mg/kg吡罗昔康或其Cu2+络合物(0.64 mg/kg吡罗昔康 + 0.12 mg/kg Cu2+)对小鼠进行腹腔注射,在减少铜绿假单胞菌肽趋化因子气溶胶激发诱导的多形核白细胞(PMNL)向气道的迁移和肺中髓过氧化物酶活性的含量方面同样有效。因此,吡罗昔康 - Cu2+络合物可能兼具吡罗昔康的抗炎活性和Cu2+的SOD样活性。

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